1. Field of the Invention
The invention concerns novel synthetic polypeptides and their use in the diagnosis and treatment of multiple sclerosis; intermediates and derivatives thereof.
2. Brief Description of the Prior Art
It has been reported that the basic protein isolated from myelin of the central nervous system of man and animals induces experimental allergic encephalomyelitis (EAE), an auto-immune disease of the central nervous system. The structure for the basic protein was published by E. H. Eylar, Steven Brostoff, George Hashim, Juanita Caccam, and Paul Burnett entitled "Basic Al Protein of the Myelin Membrane", The Journal of Biological Chemistry, Vol. 246, No. 18, Issue of Sept. 25, 1971, pp. 5770-5784. Also, it has been shown that the disease inducing basic protein is readily hydrolyzed by proteolytic enzymes. It is also known that there is more than one disease inducing region found on the native basic protein molecule. These regions have been isolated in the form of peptides following hydrolysis of the basic protein. The essential requirement for disease induction in the guinea pig is the linear sequence of at least nine amino acid residues having the schematic of formula: EQU H-Phe-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Lys-OH
for convenience, the amino acid groups in the above formula, and at times hereinafter, are referred to by abbreviations, following accepted and common practice in peptide chemistry. For example, the following abbreviations for amino acids are used, at times, throughout the following specification and claims:
Lys - lysine PA1 His - histidine PA1 Arg - arginine PA1 Thr - threonine PA1 Ser - serine PA1 Glu - glutamic acid PA1 Pro - proline PA1 Gln - glutamine PA1 Gly - glycine PA1 Ala - alanine PA1 Leu - leucine PA1 Ileu - isoleucine PA1 Tyr - tyrosine PA1 Trp - tryptophan PA1 Phe - phenylalanine
In each instance herein, it should be understood that in referring to amino acids, both the D- and L-isomeric forms are intended to be identified unless otherwise indicated.
For disease induction of guinea pigs the linear sequence of amino acid residues required is of the schematic formula: EQU H-Phe-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Arg-OH
and for disease induction in monkeys and rabbits the linear sequence of amino acid residues required is of the schematic formula: EQU H-Thr-Thr-His-Tyr-Gly-Ser-Leu-Pro-Gln-Lys-OH.
investigators have shown that EAE can be induced in animals by administering a natural compound having one of the disease inducing regions of the basic proteins. Other disease inducing peptides produced from the native basic protein by hydrolysis have been isolated. The disease induced by the active regions has the same clinical and pathological manifestations as that produced when the whole protein is administered.
Unexpectedly, the administration to a mammal of the synthetic compounds of my invention does not induce disease in the mammals as occurs upon administration of the naturally occurring analogs.